Global transcriptome characterization of peripheral blood mononuclear cells in individuals with chronic HIV infection

Acquired Immune Deficiency Syndrome (AIDS), resulting from Human Immunodeficiency Virus (HIV) infection, is one of the most severe infectious diseases worldwide. The current state of prevention and control remains critical. Recent studies have increasingly highlighted the significant role of cellular metabolism in regulating immune responses and managing infections. However, whether distinct immunometabolic profiles exist among different groups infected with HIV remains to be investigated. In this study, we employed RNA-seq technology to explore the differential characterization of immune metabolism across various HIV infections.

To investigate the metabolic differences in peripheral blood mononuclear cells (PBMCs) from HIV-infected populations, we obtained PBMCs from 18 individuals diagnosed with HIV. This cohort included four Immune Responders (IRs), five Immune Non-Responders (INRs), five typical progressors (TPs) who maintained high viral loads, and four Elite Controllers (ECs) who sustained low levels of viral replication without treatment. We conducted single-cell sequencing on the PBMCs derived from these patients and compared the results between IRs and INRs, as well as ECs and TPs.

Our findings revealed significant metabolic dysregulation and altered inflammatory states in INRs compared to IRs. These alterations were primarily observed in purine metabolism, oxidative phosphorylation (OXPHOS) and glycolysis pathways, as well as modifications in amino acid and fatty acid metabolism pathways. Furthermore, we identified variations within a subset of CD8⁺ T-cell populations characterized by high expression of GNLY, which predominantly exerts cytotoxic effects. Differences in metabolic pathways were also noted between ECs and TPs; however, these changes mainly focused on OXPHOS and pentose phosphate pathways while no significant differences were observed in glycolysis pathway.